2014-07-17Zeitschriftenartikel DOI: 10.1371/journal.ppat.1004263
BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei
Oppenheim, Rebecca D.
Creek, Darren J.
Macrae, James I.
Modrzynska, Katarzyna K.
Barrett, Michael P.
McConville, Malcolm J.
While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens.
Dateien zu dieser Publikation
Anzeige der Publikationen mit ähnlichem Titel, Autor, Urheber und Thema.
2007-05-25ZeitschriftenartikelFepA- and TonB-dependent bacteriophage H8: receptor binding and genomic sequence. Rabsch, Wolfgang; Ma, Li; Wiley, Graham; Najar, Fares Z.; Kaserer, Wallace; Schuerch, Daniel W.; Klebba, Joseph E.; Roe, Bruce A.; Gomez, Jenny A. Laverde; Schallmey, Marcus; Newton, Salete M. C.; Klebba, Phillip E.H8 is derived from a collection of Salmonella enterica serotype Enteritidis bacteriophage. Its morphology and genomic structure closely resemble those of bacteriophage T5 in the family Siphoviridae. H8 infected S. enterica ...
2005-06-20ZeitschriftenartikelViral promoters can initiate expression of toxin genes introduced into Escherichia coli Lewin, Astrid; Mayer, Martin; Chusainow, Janet; Jacob, Daniela; Appel, BerndBackground: The expression of recombinant proteins in eukaryotic cells requires the fusion of the coding region to a promoter functional in the eukaryotic cell line. Viral promoters are very often used for this purpose. ...
2013-08-08ZeitschriftenartikelCytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response Stahl, Sebastian; Burkhart, Julia M.; Hinte, Florian; Tirosh, Boaz; Mohr, Hermine; Zahedi, René P.; Sickmann, Albert; Ruzsics, Zsolt; Budt, Matthias; Brune, WolframDuring viral infection, a massive demand for viral glycoproteins can overwhelm the capacity of the protein folding and quality control machinery, leading to an accumulation of unfolded proteins in the endoplasmic reticulum ...